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Journal of Virology, November 2002, p. 11033-11041, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.11033-11041.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Productive Infection of Plasmacytoid Dendritic Cells with Human Immunodeficiency Virus Type 1 Is Triggered by CD40 Ligation

Lawrence Fong,1* Manuela Mengozzi,2 Nancy W. Abbey,3 Brian G. Herndier,3 and Edgar G. Engleman1

Department of Pathology,1 Department of Genetics, Stanford University School of Medicine, Stanford, California 94304,2 Department of Pathology, University of California, San Francisco, California 941103

Received 18 March 2002/ Accepted 19 July 2002

Immature plasmacytoid dendritic cells are the principal alpha interferon-producing cells (IPC), responsible for primary antiviral immunity. IPC express surface molecules CD4, CCR5, and CXCR4, which are known coreceptors required for human immunodeficiency virus (HIV) infection. Here we show that IPC are susceptible to and replicate HIV type 1 (HIV-1). Importantly, viral replication is triggered upon activation of IPC with CD40 ligand, a signal physiologically delivered by CD4 T cells. Immunohistochemical staining of tonsil from HIV-infected individuals reveals HIV p24+ IPC, consistent with in vivo infection of these cells. IPC exposed in vitro to HIV produce alpha interferon, which partially inhibits viral replication. Nevertheless, IPC efficiently transmit HIV-1 to CD4 T-cells, and such transmission is also augmented by CD40 ligand activation. IPC produce RANTES/CCL5 and MIP-1{alpha}/CCL3 when exposed to HIV in vitro. IPC also induce naïve CD4 T cells to proliferate and would therefore preferentially infect these cells. These results indicate that IPC may play an important role in the dissemination of HIV.

* Corresponding author. Mailing address: Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, HSW 513, Box 0511, 513 Parnassus Ave., San Francisco, CA 94143-0511. Phone: (415) 514-3160. Fax: (415) 514-3165. E-mail: lfong{at}medicine.ucsf.edu.

Journal of Virology, November 2002, p. 11033-11041, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.11033-11041.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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